Behind every breakthrough in Alzheimer’s disease treatments is a long journey of testing, refinement and learning. Each clinical trial phase builds on the last and assists researchers moving from possibility to proof. Randomized clinical trials are the “gold standard” in research and are considered the most reliable methods for determining the effectiveness of a treatment. Here’s how clinical trial phases work, and why it matters.

Building blocks: How the phases work

You’ve likely read or heard about Alzheimer’s clinical trials in various phases—I, II, III and IV. But, what do they mean?

The clinical trials process starts off with a small group of participants in Phase I, the first stage of human testing. Then, if results remain positive, it will progress through Phase II followed by Phase III, with an increasing number of participants at each stage. If a drug successfully completes the first three phases, it still requires approval from a country’s health authority before it is available for doctors to prescribe to patients. In this United States, this agency is the Food and Drug Administration (FDA). If the treatment is approved for use, Phase IV trials are often required by the health authority to monitor long-term safety and effectiveness. Across every phase of a clinical trial, participants are carefully monitored and receive ongoing medical evaluations to ensure their safety and well-being.

Let’s take a closer look at the process:

Phase I:

• Size of trial: Typically involves less than 100 participants who are often healthy volunteers.
• What this stage evaluates: It looks at the risks and side effects of the drug. During the trial, participants may receive treatment in increasing doses to understand the safety and tolerability of different doses.
• Duration: Several months.

Phase II:

• Size of the trial: Enrolls up to a few hundred participants who have the condition the drug is intended to address.
• What this stage evaluates: Phase II studies offer initial insights into the efficacy of the drug and provide additional information about safety. However, these trials are typically too small to definitively show evidence about its benefits.
• Duration: Several months to a year.

Phase III:

• Size of the trial: Several hundred to thousands of volunteers enroll, often at multiple study sites worldwide.
• What this stage evaluates: This phase offers key evidence into the safety and effectiveness of the treatment. This stage also allows researchers to compare the results against treatments that are already publicly available. This information is used by the health authority during their approval process.
• Duration: One to five years.

Phase IV (also called post-marketing studies):

• Size of the trial: Thousands of patients over an extended period of time.
• What this stage evaluates: This research occurs after health authority approval and offers a look at the long-term effects of the treatment, including its safety and effectiveness, in various populations.
• Duration: Several years.

How phased trials protect patients and advance science

Phased trials serve as the bridge between scientific discovery and every day care allowing Alzheimer’s disease treatments to be proven in practice across diverse groups in real-world conditions. Ultimately, this approach ensures that only effective Alzheimer’s treatments reach the public. As a result of this in-depth process, you can rest assured that the treatment has passed rigorous testing to ensure its safety and effectiveness.

If a phase is determined to be unsuccessful, for reasons ranging from safety concerns or intolerable side effects to not outperforming existing options or failing to meet statistical benchmarks, then the trial will not move to the next stage. Even if this happens, it’s important to remember that all trials still help researchers gather critical information. Clinical trials are solely responsible for what we know about current and potential Alzheimer’s treatments. This includes trials that did not achieve their expected results.

Access to trials through the Alzheimer’s Prevention Registry

While research continues to make great strides, there is a need to ensure there are enough people willing to participate in the research process. In fact, approximately 80% of studies are delayed because too few people sign up.

That’s where the Alzheimer’s Prevention Registry comes in. The goal is to connect researchers with people who are willing to help advance their work. By signing up and encouraging your family and friends to do the same, you can make a difference in the fight against Alzheimer’s disease. You’ll also have the opportunity to take part in research studies. Study participation is always optional, and your personal information will always remain confidential.

The Registry primarily contains Phase III trials and occasionally Phase II, and offers online and in-person studies with many looking for healthy volunteers. Your participation could help unlock important discoveries that will continue our progress to find a cure for Alzheimer’s disease.